Qu Dan, Xu Xiao-Man, Zhang Meng, Jiang Ting-Shu, Zhang Yi, Li Sheng-Qi
Department of Respiratory Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Department of Geriatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Mol Med Rep. 2015 Jul;12(1):1305-13. doi: 10.3892/mmr.2015.3510. Epub 2015 Mar 18.
Shikonin, a naturally occurring naphthoquinone, exhibits anti-tumorigenic activity. However, its precise mechanisms of action have remained elusive. In the present study, the involvement in the action of shikonin of the ubiquitin ligases Cbl-b and c-Cbl, which are negative regulators of phosphoinositide 3-kinase (PI3K) activation, was investigated. Shikonin was observed to reduce cell viability and induce apoptosis and G2/M phase arrest in lung cancer cells. In addition, shikonin increased the protein levels of B-cell lymphoma 2 (Bcl-2)-associated X and p53 and reduced those of Bcl-2. Additionally, shikonin inhibited PI3k/Akt activity and upregulated Cbl protein expression. In addition, a specific inhibitor of PI3K, LY294002, was observed to have a synergistic effect on the proliferation inhibition and apoptotic induction of A549 cells with shikonin. In conclusion, the results of the present study suggested that Cbl proteins promote shikonin-induced apoptosis by negatively regulating PI3K/Akt signaling in lung cancer cells.
紫草素是一种天然存在的萘醌，具有抗肿瘤活性。然而，其确切的作用机制仍不清楚。在本研究中，研究了泛素连接酶Cbl-b和c-Cbl（它们是磷酸肌醇3-激酶（PI3K）激活的负调节因子）在紫草素作用中的参与情况。观察到紫草素可降低肺癌细胞的活力，诱导细胞凋亡和G2/M期阻滞。此外，紫草素增加了B细胞淋巴瘤2（Bcl-2）相关X蛋白和p53的蛋白水平，并降低了Bcl-2的蛋白水平。此外，紫草素抑制PI3k/Akt活性并上调Cbl蛋白表达。此外，观察到PI3K的特异性抑制剂LY294002与紫草素对A549细胞的增殖抑制和凋亡诱导具有协同作用。总之，本研究结果表明，Cbl蛋白通过负调节肺癌细胞中的PI3K/Akt信号传导来促进紫草素诱导的细胞凋亡。
